Anatomic pathology selected abstracts

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Correspondence: Dr. Parham Minoo at parham.minoo@albertaprecisionlabs.ca

Interobserver variability in measuring depth of submucosal invasion of esophageal adenocarcinoma

Emerging data indicate that submucosa-invasive (pT1b) esophageal adenocarcinomas can be cured via endoscopic resection provided that invasion measures 500 μm or less and the adenocarcinomas lack other histological features predictive of nodal metastasis and exhibit negative margins. Therefore, pathologists’ measurements of the depth of submucosal invasion in endoscopic resections may dictate management—that is, endoscopic follow-up versus oesophagectomy. The authors assessed interobserver agreement in measuring the depth of submucosal invasion in oesophageal endoscopic resections. For their study, six subspecialized gastrointestinal pathologists from five academic centers independently measured the depth of submucosal invasion in micrometers from the deepest muscularis mucosa on 37 oesophageal endoscopic resection slides (round one scoring). They then participated in a meeting to discuss a consensus approach to measuring depth of invasion and assess potential pitfalls. Remeasuring (round two scoring) was conducted after the consensus meeting. Intraclass correlation coefficient (ICC) and Cohen’s kappa statistics were used to assess interobserver agreement. A lack of agreement was seen among the six reviewers with poor ICC for rounds one (0.40; 95 percent confidence interval [CI], 0.26–0.56) and two (0.49; 95 percent CI, 0.34–0.63). When measurements were categorized as greater or less than 500 μm, overall agreement among the six reviewers was only fair for rounds one (κ=0.37, 95 percent CI, 0.22–0.53) and two (κ=0.29, 95 percent CI, 0.12–0.46). The authors concluded that this study shows a lack of agreement among gastrointestinal pathologists in measuring the depth of submucosal invasion in oesophageal endoscopic resections despite formulating a consensus approach for scoring. If important management decisions continue to be based on this parameter, more reproducible and concrete guidelines are needed.

Karamchandani DM, Gonzalez RS, Westerhoff M, et al. Measuring depth of invasion of submucosa–invasive adenocarcinoma in oesophageal endoscopic specimens: how good are we? Histopathology. 2022;80(2):420–429.

Correspondence: Dr. D. M. Karamchandani at mahajan.dipti@gmail.com

Limited adenocarcinoma of the prostate on needle core biopsy

Grading small foci of prostate cancer on a needle biopsy is often difficult, and the clinical significance of accurate grading remains uncertain. The authors conducted a study to assess whether grading limited adenocarcinoma on prostate biopsy specimens is critical. They assessed 295 consecutive patients who had one-core involvement of adenocarcinoma and had undergone extended sextant biopsy followed by radical prostatectomy. The linear tumor lengths on the biopsy specimens were less than 1 mm (n=114), 1 mm to 2 mm (n=82), 2 mm to 3 mm (n=35), and 3 mm or more (n=64). Longer length was strongly associated with higher grade group on biopsy or prostatectomy specimens, higher risk of extraprostatic extension or seminal vesicle invasion and positive surgical margin, and larger estimated tumor volume. When cases were compared based on biopsy specimen grade group, higher grade was strongly associated with higher prostatectomy specimen grade group, higher incidence of pT3/pT3b disease, and larger tumor volume. Outcome analysis further showed significantly higher risks for biochemical recurrence after radical prostatectomy in patients with 1 mm or more, 2 mm or more, 3 mm or more, GG2-4, GG3-4, GG4, less than 1 mm/GG2-4, less than 1 mm/GG3-4, less than 2 mm/GG3-4, 3 mm or more/GG2-4, or 3 mm or more/GG3-4 tumor on biopsy specimens than in respective control subgroups. In particular, 3 mm or more, GG3, and GG4 on biopsy specimens showed significance as independent prognosticators by multivariate analysis. No significant differences were noted in the rate of upgrading or downgrading after radical prostatectomy among those subgrouped by biopsy specimen tumor length—that is, less than 1 mm (44.7 percent), 1 mm to 2 mm (41.5 percent), 2 mm to 3 mm (45.7 percent), and 3 mm or more (46.9 percent). These results indicate that pathologists should make every effort to grade relatively small prostate cancer on biopsy specimens.

Bell PD, Teramoto Y, Gurung PMS, et al. Limited adenocarcinoma of the prostate on needle core biopsy: Is grading critical? Arch Pathol Lab Med. 2022;146(4):469–477.

Correspondence: Dr. Hiroshi Miyamoto at hiroshi_miyamoto@urmc.rochester.edu

Characterization of features of colonic injury in patients receiving tacrolimus

Tacrolimus is a common immunosuppressant used in solid organ transplant recipients. Although it has been reported that most patients develop symptoms of diarrhea, there are limited data regarding patterns of injury in patients taking the immunosuppressant. The authors performed a study to characterize tacrolimus-related features of colonic injury. They retrospectively identified colonic samples from 20 patients receiving tacrolimus monotherapy. Records were reviewed for symptoms, endoscopic findings, other medications, and infections. None of the patients had gastrointestinal infections or used other drugs known to cause colonic injury, and none had received mycophenolate within six months of presentation. Cases were evaluated for the nature and distribution of inflammation and crypt abnormalities, including distortion, destruction, and apoptosis. Eighteen of the 20 (90 percent) patients were solid organ transplant recipients, and 17 of the 20 (85 percent) had gastrointestinal symptoms, most often diarrhea (75 percent). Furthermore, more than 50 percent had endoscopic colitis and 15 percent had ulcers or erosions, or both. Most (90 percent) cases showed regenerative epithelial changes. Apoptotic crypt cells were present in 55 percent of cases and numerous in 10 percent. Neutrophilic cryptitis was present in 60 percent of cases, and 35 percent showed crypt destruction. Plasma cell-rich lamina propria inflammation and crypt distortion were observed in 40 percent and 25 percent of cases, respectively. There was no correlation between therapy duration and features of chronic injury. The authors concluded that tacrolimus can cause symptomatic colitis. Histologic abnormalities are often mild and include regenerative crypts and scattered apoptotic debris. However, 40 percent of symptomatic patients have chronic colitis, most likely reflecting drug-induced immune dysregulation. Pathologists should be aware of these associations because colitis often resolves with decreasing drug dosage rather than treatment directed toward inflammatory bowel disease.

Hissong E, Mostyka M, Yantiss RK. Histologic features of tacrolimus-induced colonic injury. Am J Surg Pathol. 2022;46(1):118–123.

Correspondence: Dr. Erika Hissong at ehissong@med.umich.edu